Risk factors for joint symptoms identified

Several variables put postmenopausal women with breast cancer at higher risk.

Previous hormone therapy, hormone receptor positivity, previous chemotherapy, obesity and treatment with anastrozole were risk factors for joint symptoms in postmenopausal women, according to researchers from the United Kingdom.

The researchers analyzed data from 5,433 women from the Arimidex Tamoxifen Alone or in Combination trial. Participants who started their allocated treatment and who did not have joint symptoms at entry were randomly assigned to anastrozole (n=2,698) or tamoxifen (n=2,735).

“The Arimidex Tamoxifen Alone or in Combination trial findings showed that anastrozole [Arimidex, AstraZeneca] induced significantly more joint symptoms than tamoxifen,” Ivana Sestak, PhD, statistician at the Center for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine in London, told Endocrine Today.

“However, it is not the only factor influencing their incidence, and other factors such as previous hormone replacement therapy use, obesity or previous chemotherapy in these breast cancer patients actually led to a greater increase in joint symptoms than use of the aromatase inhibitor anastrozole,” she said.

The findings were published in The Lancet Oncology.

Several risk factors observed

More women who used HT (n=777 of 1,914) developed joint symptoms compared with women who did not use HT (n=1,001 of 3,519; OR=1.72; 95% CI, 1.53-1.93).

Women with hormone receptor–negative breast cancer (n=124 of 461) developed fewer joint symptoms than women with hormone receptor–positive tumors (n=1,556 of 4,548; OR=0.71; 95% CI, 0.57-0.88), according to the researchers.

Women who previously received chemotherapy (n=461 of 1,219) developed more joint symptoms than women who had not received it (n=1,317 of 4,214; OR=1.34; 95% CI, 1.17-1.53).

BMI .30 (n=504 of 1,354) was associated with more joint symptoms than BMI 25 to 30 (n=502 of 1,926; OR=1.01; 95% CI, 0.88-1.16) or BMI ,25 (n=592 of 1,908; OR=1.32; 95% CI, 1.14-1.53), according to the researchers.

Women assigned to anastrozole (n=949 of 2,698) had more joint symptoms vs. women assigned to tamoxifen (n=829 of 2,735; OR=1.25; 95% CI, 1.11-1.40).

“The effect of the different risk factors was additive, so it is important to take them into account when prescribing an aromatase inhibitor and when counseling women as to the possibility of experiencing joint symptoms,” Sestak said. “It is also important to indicate that in most cases symptoms were mild and disappeared spontaneously during a period of three to six months. For the few women who experience severe or long-lasting symptoms, switching to tamoxifen is a reasonable alternative.” – by Christen Haigh

Lancet Oncol. 2008;doi:10.1016/S1470-2045(08)70182-7.

It is clear that joint symptoms were a limiting toxicity for some women treated with aromatase inhibitors. These researchers showed that some clinical factors predicted women at higher risk for developing symptoms, but the clinical utility of these predictive factors is uncertain. Even in the most favorable group, greater than 30% of women reported joint symptoms, and it would be hard to use these factors to make a decision between aromatase inhibitors and tamoxifen. However, these findings, coupled with a small study whose results showed that aromatase inhibitors were associated with decreased hand grip strength and tenosynovial changes (J Clin Oncol. 2008;26:3147-3152), demonstrate that serious joint and articular changes occur during aromatase inhibitor use. Since compliance to endocrine therapy is critical, physicians should discuss these symptoms with their patients receiving adjuvant aromatase inhibitors.

– Douglas Yee, MD

Director, University of Minnesota Cancer Center, Minneapolis

These data correlate some of the biology of breast cancer and obesity with an increased risk for joint symptoms, but they are not that impactful for practice or for the decision to use aromatase inhibitors or tamoxifen. However, they should help with patient education.

– Edith A. Perez, MD

Professor of Medicine, Hematology/Oncology, Mayo Clinic, Jacksonville, Fla.